The non-medical use of prescription opioids continues to escalate in the United States, as reflected in a variety of sources. In order to better understand this national phenomenon, recent work in our laboratory has begun to characterize the reinforcing and subjective effects of prescription opioids in humans. A study conducted during our previous award period revealed that oral oxycodone elicited similar subjective effects in drug abusers and non-drug abusers, but the self-administration patterns differed between these two groups as a function of pain. Specifically, non-drug abusers only self-administered oxycodone when they experienced experimentally induced pain, while abusers self-administered oxycodone regardless of pain condition. In another study conducted in our laboratory under another grant, we found that the effects of oral oxycodone and oral morphine differed in heroin-dependent individuals who were maintained on sublingual buprenorphine. Specifically, both oxycodone and morphine were self-administered more than placebo using a drug versus drug self-administration choice procedure, yet morphine was not well liked. Further, when the effects of morphine and oxycodone were compared directly, participants chose to self-administer oral oxycodone significantly more than oral morphine. This finding suggests that when given orally, oxycodone was preferred over, and may be more likely to be abused than, morphine in heroin-dependent individuals. Whether or not this asymmetrical relationship between oxycodone and morphine also exists in prescription-opioid abusing individuals who are in chronic pain versus those who are not in chronic pain is unknown, as this direct comparison has not yet been investigated under the same experimental conditions. Therefore, the study proposed in the current application will examine the effects of oral oxycodone and morphine in 4 groups of participants who will be maintained on sublingual buprenorphine/naloxone: heroin abusers who are not in pain, prescription opioid abusers who are not in pain, patients with chronic pain who are abusing prescription opioids, and patients with chronic pain who are not abusing prescription opioids. It is vitally important to include this last group of participants when attempting to gain a complete picture of the relationship between pain and prescription-opioid abuse. By including this group of patients, we may begin to disentangle to what extent the problems of prescription opioid misuse are related to the pharmacological properties of these drugs, the presence or absence of clinical pain, and the presence or absence of drug abuse. Participants will be maintained on three doses of sublingual buprenorphine/naloxone (2/0.5 mg, 16/4 mg, 32/8 mg). The relative reinforcing effects of oxycodone and morphine will be tested under each sublingual buprenorphine/naloxone maintenance dose condition. Findings will inform both the substance abuse literature as well as the pain literature. PUBLIC HEALTH RELEVANCE: The misuse of prescription opioid medications among individuals with pain, as well as those without pain, is of significant concern to the public health of the nation. However, the study of prescription opioid abuse in different populations of patients is in its infancy. This study proposes to examine the relative abuse liability of 2 commonly prescribed opioids in 4 groups of participants who will be maintained on sublingual buprenorphine/naloxone: heroin abusers and who are not in pain, prescription opioid abusers who are not in pain, patients with chronic pain who are abusing prescription opioids, and patients with chronic pain who are not abusing prescription opioids.